Trends in Genetics
ReviewChecking cell size in yeast
Section snippets
Size control at Start: budding yeast
How does budding yeast measure its size, and how does this control Start? The G1–S size-control module is presented in Fig. 2. Its core consists of three G1 cyclins (Cln1–3) and two B-type cyclins (Clb5 and Clb6). These cyclins bind to a CDK1 homolog, Cdc28 (Table 1), and target its activity towards specific sets of substrates. The level of Cln3 is important for timely expression of the CLN1 and CLN2 genes. The resulting increase in the activity of Cln1– and Cln2–Cdc28 complexes is responsible
Size control at Start: fission yeast
In fission yeast, Start is initiated by a CDK1 homolog, Cdc2, in association with a G1 cyclin, Puc1, and three B-type cyclins, Cig1, Cig2 and Cdc13. Two inhibitory mechanisms prevent premature initiation of S phase: one involves a CDK inhibitor, Rum1, and the other involves a component of the ubiquitin proteolysis machinery, Ste9. The wiring diagram reveals striking similarity between fission yeast and budding yeast (Fig. 3, Table 1) [9]. As already mentioned, the fission yeast G1–S size
Size control at G2–M: fission yeast
The wee1 gene was isolated as the prototype cell-size mutant that enters mitosis precociously and loses the wild-type ability to modify cell size at mitosis in response to the availability of nitrogen [9]. As cells progress through S and G2, Cdc13 slowly accumulates, but the associated Cdc2 activity remains inhibited by Wee1-dependent tyrosine phosphorylation (Fig. 4a). A Wee1 inhibitory kinase, Cdr1, is probably a component of the nutrition-sensing module (Fig. 1a, process 1) as cdr1-deficient
Size control in G2–M: budding yeast
In G2, Cdc28 is phosphorylated by the Wee1 homolog Swe1, and dephosphorylated by the Cdc25 homolog Mih1 [8] (Fig. 4b, Table 1). Unlike their counterparts in fission yeast, however, neither of these components are essential in budding yeast. It has been proposed that instead of size control, Clb2–Cdc28 tyrosine phosphorylation evolved a specialized function in execution of a morphogenesis checkpoint. The checkpoint is activated when cells fail to form a bud or when the integrity of the actin
Concluding remarks
What is ‘cell size’? Entirely in accord with Pringle and Hartwell [10], I use this deliberately vague expression instead of more specific terms simply because we are still far from fully understanding what represents cell size within cells. Production of Cln3 is clearly dependent on the total number of ribosomes in the cytoplasm, which increases as cells grow, but other possible sizers do not offer such clear-cut solutions. Protein mass, the number of ribosomes and cell volume are obvious
Acknowledgements
I thank E. Boye, L. Breeden, B. Futcher, D. Kellogg, D. Lew, S. Moreno and A. Sveiczer for fruitful discussions and for sharing their data before publication. I also thank P. Young, J. Karagiannis and D. Kellogg for critical reading of the manuscript.
References (70)
- et al.
Connections between growth and the cell cycle
Curr. Opin. Cell Biol.
(1998) - et al.
Coordination of cell growth with cell division
Curr. Opin. Genet. Dev.
(1999) - et al.
Size control in animal development
Cell
(1999) - et al.
Genetic control of cell size
Curr. Opin. Genet. Dev.
(2000) A long twentieth century of the cell cycle and beyond
Cell
(2000)- et al.
Control of the timing of cell division in fission yeast. Cell size mutants reveal a second control pathway
Exp. Cell Res.
(1978) Regulation of Wee1 kinase in response to protein synthesis inhibition
FEBS Lett.
(2000)Regulation of Schizosaccharomyces pombe Wee1 tyrosine kinase
J. Biol. Chem.
(1997)A stochastic, molecular model of the fission yeast cell cycle: role of the nucleocytoplasmic ratio in cycle time regulation
Biophys. Chem.
(2001)Cell-cycle checkpoints that ensure coordination between nuclear and cytoplasmic events in Saccharomyces cerevisiae
Curr. Opin. Genet. Dev.
(2000)
Conservation of mitotic controls in fission and budding yeast
Cell
It's a noisy business! Genetic regulation at the nanomolar scale
Trends Genet.
Do growth and cell division rates determine cell size in multicellular organisms?
J. Cell Sci.
Where does fission yeast sit on the tree of life?
Genome Biol. , .1–1011.4
Cell cycle control in Saccharomyces cerevisiae
Cell cycle control in fission yeast
The Saccharomyces cerevisiae cell cycle
The size control of fission yeast revisited
J. Cell Sci.
Cyclins and the wiring of the yeast cell cycle
Yeast
Regulation of the Cln3–Cdc28 kinase by cAMP in Saccharomyces cerevisiae
EMBO J.
The Cln3 cyclin is down-regulated by translational repression and degradation during the G1 arrest caused by nitrogen deprivation in budding yeast
EMBO J.
Transcriptional regulation of CLN3 expression by glucose in Saccharomyces cerevisiae
J. Bacteriol.
AZF1 is a glucose-dependent positive regulator of CLN3 transcription in Saccharomyces cerevisiae
Mol. Cell. Biol.
Coupling of cell division to cell growth by translational control of the G1 cyclin CLN3 in yeast
Genes Dev.
The TOR (target of rapamycin) signal transduction pathway regulates the stability of translation initiation factor eIF4G in the yeast Saccharomyces cerevisiae
Proc. Natl. Acad. Sci. U. S. A.
CLN3 expression is sufficient to restore G1-to-S-phase progression in Saccharomyces cerevisiae mutants defective in translation initiation factor eIF4E
Biochem. J.
Whi3 binds the mRNA of the G1 cyclin CLN3 to modulate cell fate in budding yeast
Genes Dev.
Comparison of the Saccharomyces cerevisiae G1 cyclins: Cln3 may be an upstream activator of Cln1, Cln2 and other cyclins
EMBO J.
Testing a mathematical model of the yeast cell cycle
Mol. Biol. Cell
Distinct subcellular localization patterns contribute to functional specificity of the Cln2 and Cln3 cyclins of Saccharomyces cerevisiae
Mol. Cell Biol.
Relationship between the function and the location of G1 cyclins in S. cerevisiae
J. Cell Sci.
Roles and regulation of Cln–Cdc28 kinases at the start of the cell cycle of Saccharomyces cerevisiae
EMBO J.
CLN3, not positive feedback, determines the timing of CLN2 transcription in cycling cells
Genes Dev.
Kinetic analysis of a molecular model of the budding yeast cell cycle
Mol. Biol. Cell
A novel Mcm1-dependent element in the SWI4, CLN3, CDC6, and CDC47 promoters activates M/G1-specific transcription
Genes Dev.
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